Doctoral (PhD) student position in Liver Metastases Encapsulation: Cellular Players and Molecular Mechanisms

To be a doctoral student means to devote oneself to a research project under supervision of experienced researchers and following an individual study plan. For a doctoral degree, the equivalent of four years of full-time doctoral education is required.

The Cancer Cell Invasion Laboratory, led by Marco Gerling, studies the biological processes of tumor cell invasion at tumor-parenchymal interfaces, https://ki.se/en/bionut/cancer-cell-invasion . The group uses clinical cohorts and advanced histopathological tools, including machine learning techniques, to identify the cellular players at these interfaces. They apply single-cell sequencing and mouse models of primary and metastatic cancer to generate hypotheses of the molecular mechanisms that govern tumor cell invasion, and to test candidate pathways functionally. The group has a strong translational focus and is involved in clinical studies funded by the European Union.

Metastases are the major cause of mortality in cancer. Liver metastases are particularly common in gastrointestinal cancers and can be categorized into two histological growth patterns, encapsulated and replacement. The host group and others have shown that encapsulated metastases are associated with favorable survival. Mechanistically, the group has linked impaired tumor cell invasion to metastases encapsulation (Fernández Moro et al, Nature Communications, 2023).

This PhD project aims to understand the molecular mechanisms of the encapsulation process to develop novel therapies that could induce encapsulation.

The main questions are:

The student will use a mouse model to ablate established metastases, followed by single-cell sequencing and in situ staining techniques to validate the sc-seq results. Human samples will be used to map cellular players identified in sc-seq. Machine-learning tools will be used to quantify the results and overlay gene expression data spatially to histological images. The student will then functionally validate candidate pathways in mouse models of replacement-type and encapsulated metastases to induce or reduce encapsulation.

Uncovering the mechanisms and cellular players in the process of capsule formation in comparison with replacement-type metastases growth is expected to give key insights into the biological process behind capsule formation. Based on its translational nature, this project aims to develop targets to augment capsule formation usable for clinical interventions, which could significantly enhance the therapeutic options for liver metastases patients. 

A creative and inspiring environment full of expertise and curiosity. Karolinska Institutet is one of the world's leading medical universities. Our vision is to pursue the development of knowledge about life and to promote a better health for all. At Karolinska Institutet, we conduct successful medical research and hold the largest range of medical education in Sweden. As a doctoral student you are offered an individual research project, a well-educated supervisor, a vast range of elective courses and the opportunity to work in a leading research group. Karolinska Institutet collaborates with prominent universities from all around the world, which ensures opportunities for international exchanges. You will be employed on a doctoral studentship which means that you receive a contractual salary. Employees also have access to our modern gym for free and receive reimbursements for medical care.

In order to participate in the selection for a doctoral position, you must meet the following general (A) and specific (B) eligibility requirements at latest by the application deadline.

It is your responsibility to certify eligibility by following the instructions on the web page Entry requirements (eligibility) for doctoral education.

A) General eligibility requirement

You meet the general eligibility requirement for doctoral/third-cycle/PhD education if you:

Follow the instructions on the web page Entry requirements (eligibility) for doctoral education.

*If you claim equivalent knowledge, follow the instructions on the web page Assessing equivalent knowledge for general eligibility for doctoral education.

B) Specific eligibility requirement

You meet the specific eligibility requirement for doctoral/third-cycle/PhD education if you:

- Show proficiency in English equivalent to the course English B/English 6 at Swedish upper secondary school.

Follow the instructions on the web page English language requirements for doctoral education.

Verification of your documents Karolinska Institutet checks the authenticity of your documents. Karolinska Institutet reserves the right to revoke admission if supporting documents are discovered to be fraudulent. Submission of false documents is a violation of Swedish law and is considered grounds for legal action.

(A) and (B)can only be certified by the documentation requirement for doctoral education .

The ideal candidate has a strong interest and documented background in histopathology and the tumor biology of gastrointestinal cancers, which would build an ideal basis for the planned studies. Particular merits are documented skills in data analysis in R, histopathological annotations (image-based recognition and thorough annotation of complex histopathological structures), machine-learning tools in histopathology, and basic culture of primary cells. Knowledge of Swedish is a plus because the project involves interpreting clinical data, which are documented in Swedish. Skills in the handling of laboratory animals and in single-cell sequencing are not required and will be a major learning objective of the PhD studies. 

The doctoral student will be employed on a doctoral studentship maximum 4 years full-time.

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Submit your application and supporting documents through the Varbi recruitment system. Use the button in the top right corner and follow the instructions. We prefer that your application is written in English, but you can also apply in Swedish.

Your application must contain the following documents:

- A personal letter and a curriculum vitae
- Degree projects and previous publications, if any
- Any other documentation showing the desirable skills and personal qualities described above
- Documents certifying your general eligibility (see A above)
- Documents certifying your specific eligibility (see B above)

A selection will be made among eligible applicants on the basis of the ability to benefit from doctoral education. The qualifications of the applicants will be evaluated on an overall basis.

Karolinska Institutet uses the following bases of assessment:

- Documented subject knowledge of relevance to the area of research
- Analytical skill
- Other documented knowledge or experience that may be relevant to doctoral studies in the subject.

All applicants will be informed when the recruitment is completed.

Links:https://ki.se/en/bionut/department-of-biosciences-and-nutrition